Pathology Flashcards
Three steps of acute inflammation
Vascular: dilation of vessels
Exudative: vascular leakage of protein rich fluid
Cells recruited: neutrophil polymorphs
Causes of acute inflammation
Microbial infections e.g. bacteria
Hypersensitivity reactions e.g. parasites
Physical agents e.g. heat
Chemicals e.g. acid
Neutrophil polymorph emigration
Margination of neutrophils
Adhesion of neutrophils (pavementing)
Neutrophil emigration
Diapedesis (leukocyte extravasation)
Outcomes of acute inflammation
Resolution: complete restoration of tissues e.g. acute lobar pneumonia
Suppuration: formation of pus, leads to scarring
Organisation: replacement by granulation tissue, macrophages migrate, fibrosis occurs e.g. post-MI
Progression: causative agent is not removed, progresses to chronic
Cells involved in acute inflammation
Neutrophils: phagocytose pathogens
Monocytes: migrate to tissue and become macrophages which induce chemotaxis
Cells involved in chronic inflammation
Lymphocytes, macrophages, plasma cells
Macroscopic appearance of chronic inflammation
Chronic ulcer
Chronic abscess cavity
Granulomatous inflammation
Fibrosis
Cellular cooperation in chronic inflammation
B lymphocytes: plasma cells, antibody production
T lymphocytes: cell-mediated immunity
Macrophages: respond to chemotactic stimuli, cytokine production (interferon alpha and beta, IL1, IL6, IL8, TNF-alpha)
Granulomas
An aggregate of epithelioid histocytes (activated macrophages resembling epithelial cells)
Causes of granuloma development
TB (most common)
Leprosy
Chrons
Sarcoidosis
Granuloma and eosinophil presence
Parasite
Platelet alpha granules
Platelet adhesion e.g. production of fibrinogen, vWF
Platelet dense granules
Platelet aggregation e.g. ADP
First stage of thrombus formation
Platelet aggregation (starts the clotting cascade)
Three major causes of thrombosis (Virchow’s triad)
Reduced blood flow (stasis) e.g. immobility
Blood vessel/endothelial injury e.g. trauma, HT
Hypercoagulability e.g. smoking
Arterial thrombosis formation
Atheromatous plaque causes turbulence in blood flow
Loss of endothelial cells, exposure to collagen
Platelet adherence and activation
Thrombus: platelets > fibrin > RBCs
Grows in the direction of blood flow (propagation)
Venous thrombosis patho
Lower blood pressure in veins, atheroma do not occur
Thrombi begin at valves which produce a degree of turbulence and can be damaged e.g. stasis
Formed under low blood pressure
Mainly made of RBCs
Clinical features of arterial thrombi
Loss of pulse distal to thrombus
Area becomes cold, pale and painful
Possible gangrene
Clinical features of venous thrombi
Tender
Area becomes reddened and swollen
Complications of arterial thrombus and treatment
MI/stroke
Tx: anti-platelets e.g. aspirin
Complications of venous thrombus and treatment
DVT/PE
Tx: anti-coagulants e.g. warfarin
Pulmonary embolism
Venous emboli travel to vena cava and lodge in the pulmonary arteries
Presentation:
Acute respiratory or cardiac problems
Chest pain and shortness of breath
Ischaemic reperfusion injury
Damage to tissue during reoxygenation after a period of ischaemia
Atherosclerosis pathogenesis
High levels of LDL accumulates IN arterial wall
Macrophages and T-cells are attracted to the site of damage and take up lipid to form foam cells
Formation of fatty streak
Activated macrophages release cytokines and growth factors
Smooth muscle cell proliferation around the lipid core, thinning of tunica media
Formation of a fibrous cap (collagen)
Risk factors for atherosclerosis
Hypercholesterolaemia (prevention: statins) Smoking Hypertension Diabetes Male
Apoptosis
Programmed sequence of intracellular events leading to the removal of a cell without the release of harmful products to surrounding cells
Inhibitors of apoptosis
Growth factors
ECM
Sex steroids
Inducers of apoptosis
Glucocorticoids
Free radicals
Ionising radiation
DNA damage
Intrinsic apoptosis pathway
Mitochondrial pathway:
Biochemical stress e.g. free radicals
Bax: induces apoptosis (p35 cell cycle arrest)
Activation of caspase cascade
Extrinsic apoptosis pathway
Used by the immune system to eliminate lymphocytes
Ligand binding at death receptors on cell surface
Receptors include TNFR1 (TNF-alpha ligand) and Fas receptor (Fas ligand)
Activation of caspase cascade
Necrosis
Traumatic cell death which indices inflammation and repair
Characterised by bioenergetic failure and loss of plasma membrane
Coagulative necrosis
Most common type
Can occur in most organs but most commonly heart and kidneys
Caused by hypoxia (ischaemia)
Liquefactive necrosis
Hydrolytic enzymes
Occurs in the brain due to its lack of substantial supporting stroma e.g. stroke
Caseous necrosis
Causes a cottage cheese pattern
TB is characterised by this form of necrosis
Gangrene
Necrosis with rotting of the tissue
Affected tissue appears black due to deposition of iron sulphide (from degraded haemoglobin)
Fat necrosis
Fatty acids spill out of adipose cells
Pancreatitis
Fibrinoid necrosis
Fibrin deposits
Vasculitis
Hypertrophy
Increase in cell SIZE without cell division
E.g. muscle hypertrophy in athletes, uterine hypertrophy in pregnancy
Hyperplasia
Increase in cell number by division (mitosis)
Cannot happen in cells that don’t divide i.e. myocardial cells or nerve cells
Atrophy
Decrease in the size of an organ - can be a reduction in cell size or cell number
E.g. muscle atrophy in ALS
Metaplasia
Change in the DIFFERENTIATION of a cell
Occurs in response to alterations in the cellular environment
E.g. squamous epithelium > columnar epithelium in Barrett’s oesophagus
Dysplasia
Morphological changes seen in cells in the progression to BECOMING CANCER
Carcinogenesis
Transformation of normal cells into neoplastic (cancerous) cells through permanent genetic alterations or mutations
Why can neoplasms not arise in erythrocytes
No nuclei
Tumour
Any abnormal swelling
Carcinogen examples
Smoking - lung tumours
EBV - Burkitts lymphoma
HPV - cervical cancer
UV radiation - skin cancer
Benign tumours features
Do not invade basement membrane Exophytic (grow outwards) Low mitotic activity Circumscribed (limited to an area) Necrosis and ulceration are rare
Malignant tumours
Invade the basement membrane Endophytic (grows inwards) High mitotic activity Poorly circumscribed Necrosis and ulceration are common
Benign epithelial tumours
Papilloma (non glandular)
Adenoma (glandular secretory tissue)
Malignant epithelial tumours
Carcinoma (malignant tumour of epithelial cells)
Adenocarcinoma (malignant tumour of glandular epithelial cells)
Types of benign connective tissue tumours
Lipoma: adipocytes Rhabdomyoma: skeletal muscle Leiomyoma: smooth muscle cells Chondroma: cartilage Osteoma: bone
Malignant connective tissue tumours
Liposarcoma: adipocytes Rhabdomysaroma: skeletal muscle Leiomysaroma: smooth muscle cells Chondrsaroma: cartilage Ostesarcoma: bone
Metastasis
which cancer never metastasises?
Malignant tumours spread from their site of origin to form other tumours at distant cites
Basal cell carcinoma NEVER metastasises
Bone metastasises from
Lung, breast, kidney, thyroid, prostate
Carcinomas preferred route
Lymphatic spread
Sarcoma preferred route
Haematogenous spread
Define inflammation
A local physiological response to injury
Most common cause of chronic inflammation
Primary chronic inflammation
Epitheliod histiocytes
Activated macrophages that resemble epithelial cells
Aggregation = granuloma
Sarcoidosis
Occurs when inflammatory cells clump together to form granulomas
Blood marker in the investigation if sarcoidosis
Serum ACE
Sequence of events in metastasis
Invasion: erosion of tissue boundaries
Intravasion: gain access to metastatic routes e.g. lymph
Evasion of host defence
Adherence to endothelium
Extravasation: colonisation of new site
Angiogenesis: develops its own blood supply
Primary pulmonary neoplasm to liver, via which spread?
Haematogenous spread
Bcl-2 role in apoptosis
Inhibits apoptosis
CO2 reading on an ABG
Same direction as pH = metabolic
Opposite direction = respiratory
